The yeast cell wall is a complex network of different macromolecules, wherein polysaccharides represent the main fraction accounting for over 50% of the cells' dry weight. Mannose- and glucose-containing polysaccharides are the major components of the yeast cell wall, with lower amounts of chitin that is usually present in the form of a chitin-glucan complex. Chitin-glucan complex (CGC) is comprised of chitin (a polymer of N-acetylglucosamine units) covalently linked to β-1,3-glucans (polymer of glucose units). This copolymer has an important structural function in the yeast cell and is water insoluble. Mannose- and glucose-containing polysaccharides include mannans (polymer of mannose units), glucans (polymer of glucose units), glucomannans (polymer of mannose and glucose units) and/or galactomannans (polymer of mannose and galactose units).
Due to its composition, the yeast cell wall is a valuable source of different types of polysaccharides, including mannans, glucomannans, galactomannans, glucans, chitin and chitin-glucan complex. Polysaccharides with similar composition can also be extracted from algae, plants or animals, such as, for example, carrageenan, guar gum and chitin. However, extraction of the polysaccharides from such higher organisms (algae, plants or animals) presents many constraints: they are dependent on seasonal production, with highly variable quality and quantity, making production process particularly irreproducible. In the case of extraction of chitin from crustaceous, the resulting products can contain toxins or allergens that render them unsuitable for human uses. On the other hand, extraction from yeasts, cultivated under controlled conditions, is far more reliable, sustainable and safe.
Recently, U.S. Pat. No. 7,556,946 and Patent application US 2010/0221382, US 2010/0003292 and WO 2010/013174 disclose methods for the preparation of cell wall derivatives from fungal or yeast biomass to obtain chitin polymers or chitin-glucan polymers.
However, the methods are focused on the production of mostly chitin- and chitosan-rich polymers, without taking advantage of the presence of other polysaccharides such as mannans, glucomannans and galactomannans.
On the other hand, other documents, such as, for example, U.S. Pat. No. 6,444,448 and Patent Applications EP 2272876 and WO 2010/070207, disclose methods for obtaining glucans and mannans from different natural sources, including bacteria, fungi, yeast and plants. Such methods rely on enzymatic (EP 2272876) or autolytic (U.S. Pat. No. 6,444,448) treatments, or on a combination of acid and alkaline treatments (2010/070207).
Excipients are ingredients used by the pharmaceutical industry to formulate active ingredients into finished dosage forms. Formulation of active pharmaceutical ingredients (APIs) with excipients is primordial to ensure an efficient drug delivery with the desired properties, together with a robust manufacturing process. Essentially, excipients are used to provide a matrix in which the drug can be handled to control the rate of dosage, to aid in the processing of the drug delivery system during its manufacture and assist in product identification, protect, support or enhance stability, bioavailability or patient acceptability, and to enhance any other attribute of the overall safety, effectiveness or delivery of the drug during storage or use.
The principal categories of excipients are binders and fillers, disintegrants, diluents, lubricants and glidants, preservatives and antioxidants. Ranging from 15% to 99% of the total weight of a given drug, excipients are extremely relevant for the drug production process, in terms of procurement, logistics, quality control and process productivity. Consequently, excipients must be able to deliver high-functionality advantages to the formulator, such as increased lubricity, improved flowability, enhanced compressibility and compatibility, improved product characteristics and sustainable production process.
As an example, the preparation of tablet dosage forms with acceptable physicochemical properties involves the use of fillers, binders, glidants and lubricants, mentioned above. In order to be compressed into tablets, such materials must have specific physical properties, namely, they must be free flowing, cohesive and lubricated. Moreover, for the release of the active pharmaceutical ingredient, a disintegrant is added to facilitate the breakup of the solid dosage form.
Although the traditional tablet components have long-established efficacy, some of them have disadvantages that are related to their cost, moderate efficiency and often time consuming excipients processes. Hence, there is a need for new excipient formulations that overcome these disadvantages. One great advantage would be the possibility of using a high functionally excipient that combines in itself the properties of different traditional excipient components, thus making the formulation process easier and faster.
Currently, most traditional excipients are synthesized or chemically modified using natural molecules as starting points. Cellulose or starch derivatives, synthetic polymers and alcohols are just a few examples that a person skilled in the art will easily identify. The use of entirely natural excipients in the pharmaceutical industry remains limited. However, these natural excipients have the advantage of being safe, non-toxic, biocompatible and biodegradable. In view of this, natural polysaccharides can be used for the development of versatile excipients with improved properties. They can be extracted from various origins, such as plants, animals or even microorganisms.
Among the natural polysaccharides emerging today as excipients, people skilled in the art will identify polymers, such as guar gum or carrageenans. Guar gum, used as thickener for lotions and creams, as a tablet binder or as an emulsion stabilizer, is a galactomannan (polymer of galactose and mannose units), which occurs as a storage polysaccharide in the seed endosperm of some plants. Carrageenans are the generic name for a family of high molecular weight sulphated polysaccharides obtained from certain species of red seaweeds, suitable for tablet manufacturing.